In Deinococcus radiodurans and other resistant bacteria, a mechanistic link exists between resistance, manganese accumulation, and protein protection. We previously demonstrated that ultrafiltered, protein-free preparations of D. radiodurans cell extracts prevent protein oxidation at massive doses of ionizing radiation. The two key protective components of the extract were peptides/amino acids and manganese. Although published reports from other laboratories have proposed that manganese is critical to the resistance mechanism, our studies have found the effect to be rather modest. The differences may well be a result of different experimental approaches to altering manganese availability and uptake. Our current investigations are aimed at critically testing the manganese hypothesis. We expect to complete these studies before the end of calendar 2015, after which this project will become inactive.